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Functional analysis of clock genes in invasive breast carcinoma

Research Project

Project/Area Number 17K17575
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General surgery
Human pathology
Research InstitutionJichi Medical University (2019)
Hirosaki University (2017-2018)

Principal Investigator

Wu Yunyan  自治医科大学, 医学部, ポスト・ドクター (40636586)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords時計遺伝子 / がん微小環境 / 上皮間葉転換 / 乳癌 / 脈管新生 / 癌微小環境 / 血管新生 / 三次元培養
Outline of Final Research Achievements

The present study declares the mechanisms that clock genes, DEC1 and DEC2, regulate the epithelial-mesenchymal transition (EMT) process.
First, DEC1 overexpression upregulated podoplanin expression in carcinoma cells whereas DEC2 overexpression inhibited podoplanin. Second, the expression of DEC1 was induced when exposed to hypoxic environment. Subsequently, DEC1 promoted the EMT process by inhibiting the expression of epithelial marker E-cadherin. Third, DEC1 and DEC2 functioned as regulators of the TGFβ-Smad signaling pathway to affect EMT process in carcinoma cells. Finally, we analyzed the morphological changes by observing under transmission electron microscope (TEM). Carcinoma cells were applied on the three-dimensional tissue models and were collected at different time points. A fibroblast-like change was observed when carcinoma cells infiltrating to the stromal lymphatic vessel.

Academic Significance and Societal Importance of the Research Achievements

癌の悪性形質を制御する時計遺伝子(DEC1、DEC2)の機能を解明することにより、DEC1とDEC2を標的とする新たながん治療法(時計遺伝子DEC阻害剤薬)の開発と臨床応用研究への発展の可能性が期待できる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2019 2018 2017

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Type I Collagen Induces DEC Expression and Epithelial-Mesenchymal Transition (EMT) in Human Breast Cancer MCF-7 Cells.2019

    • Author(s)
      Tsugeno Y, Yoshizawa T, Wu Y, Goto S, Haga T, Suzuki T, Seino H, Morohashi S, Kijima H.
    • Journal Title

      BioMed Research Journal

      Volume: 3 Pages: 125-131

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histopathological Characteristics of Pancreatic Cancer Stroma Induced by Neoadjuvant Chemotherapy2019

    • Author(s)
      Goto S, Ishido K, Yoshizawa T, Haga T, Morohashi S, Wu Y, Seino H, Hakamada K, Kijima H.
    • Journal Title

      BioMed Research Journal

      Volume: 3 Pages: 61-64

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BHLH Transcription Factors DEC1 and DEC2: From Structure to Various Diseases2018

    • Author(s)
      Yunyan Wu, Hiroshi Kijima
    • Journal Title

      BioMed Research Journal

      Volume: 2 Pages: 28-33

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DEC1 and DEC2 Regulate Apoptosis of Human Prostate Adenocarcinoma LNCap Cells2018

    • Author(s)
      Qiang Liu、 Yunyan Wu、 Hiroko Seino、 Tadashi Yoshizawa、 Toshihiro Haga、 Satoko Morohashi、 Hiroshi Kijima
    • Journal Title

      BioMed Research Journal

      Volume: 1 Pages: 6-11

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correlation between DEC1/DEC2 and epithelial-mesenchymal transition in human prostate cancer PC-3 cells2018

    • Author(s)
      Liu Qiang、Wu Yunyan、Seino Hiroko、Haga Toshihiro、Yoshizawa Tadashi、Morohashi Satoko、Kijima Hiroshi
    • Journal Title

      Molecular Medicine Reports

      Volume: 4 Pages: 3859-3865

    • DOI

      10.3892/mmr.2018.9367

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neoangiogenesis of gastric submucosa-invasive adenocarcinoma2018

    • Author(s)
      Sasaki Hanae、Morohashi Satoko、Toba Takahito、Seino Hiroko、Yoshizawa Tadashi、Hirai Hideaki、Haga Toshihiro、Wu Yunyan、Kijima Hiroshi
    • Journal Title

      Oncology Letters

      Volume: 3 Pages: 3895-3900

    • DOI

      10.3892/ol.2018.9116

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of cancer-associated fibroblast markers in advanced colorectal cancer2018

    • Author(s)
      Nishishita Rie、Morohashi Satoko、Seino Hiroko、Wu Yunyan、Yoshizawa Tadashi、Haga Toshihiro、Saito Kensuke、Hakamada Kenichi、Fukuda Shinsaku、Kijima Hiroshi
    • Journal Title

      Oncol Lett.

      Volume: 15 Pages: 6195-6202

    • DOI

      10.3892/ol.2018.8097

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DEC2 expression antagonizes cisplatin-induced apoptosis in human esophageal squamous cell carcinoma2017

    • Author(s)
      Sato Hidenobu、Wu Yunyan、Kato Yukio、Liu Qiang、Hirai Hideaki、Yoshizawa Tadashi、Morohashi Satoko、Watanabe Jun、Kijima Hiroshi
    • Journal Title

      Mol Med Rep.

      Volume: 16 Issue: 1 Pages: 43-48

    • DOI

      10.3892/mmr.2017.6571

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>DEC1 promotes hypoxia-induced epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma </b><b>cells </b>2017

    • Author(s)
      Murakami Keishu、Wu Yunyan、Imaizumi Tadaatsu、 Aoki Yuka、Liu Qiang、Yan Xu、Seino Hiroko、Yoshizawa Tadashi、Morohashi Satoko、Kato Yukio、Kijima Hiroshi
    • Journal Title

      Biomedical Research

      Volume: 38 Issue: 4 Pages: 221-227

    • DOI

      10.2220/biomedres.38.221

    • NAID

      130005966980

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] <b>DEC1 negatively regulates the expression of CXCL10 and CCL5 induced by poly IC in normal human mesangial </b><b>cells </b>2017

    • Author(s)
      Liu Q, Imaizumi T, Murakami K, Tanaka H, Wu Y, Yoshizawa T, Morohashi S, Seino H, Kijima H
    • Journal Title

      Biomedical Research

      Volume: 38 Issue: 4 Pages: 249-255

    • DOI

      10.2220/biomedres.38.249

    • NAID

      130005966979

    • ISSN
      0388-6107, 1880-313X
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic Impact of CD163+ Macrophages in Tumor Stroma and CD8+ T-Cells in Cancer Cell Nests in Invasive Extrahepatic Bile Duct Cancer.2017

    • Author(s)
      Miura T, Yoshizawa T, Hirai H, Seino H, Morohashi S, Wu Y, Wakiya T, Kimura N, Kudo D, Ishido K, Toyoki Y, Kijima H, Hakamada K.
    • Journal Title

      Anticancer Res

      Volume: 37 Issue: 1 Pages: 183-190

    • DOI

      10.21873/anticanres.11304

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic Impact of Extracapsular Lymph Node Invasion and Myofibroblastic Activity in Extrahepatic Bile Duct Cancer2017

    • Author(s)
      Yoshizawa Tadashi、Ishido Keinosuke、Saito Kensuke、Haga Toshihiro、Seino Hiroko、Wu Yunyan、Morohashi Satoko、Hakamada Kenichi、Kijima Hiroshi
    • Journal Title

      Clin Med Insights Pathol.

      Volume: 10 Pages: 1-7

    • DOI

      10.1177/1179555717729652

    • NAID

      120006583346

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] BHLH transcription factors DEC1 and DEC2: From structure to various diseases.2019

    • Author(s)
      Wu Y
    • Organizer
      International Conference on Biomedical and Cancer Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DEC1 and DEC2 regulate apoptosis in human prostate cancer cells2018

    • Author(s)
      Yunyan Wu, Qiang Liu, Hiroko Seino, Shintaro Goto, Toshihiro Haga, Tadashi Yoshizawa, Hiroshi Kijima
    • Organizer
      第107回 日本病理学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] DEC1 negatively regulates expression of CXCL10 and CCL5 induced by poly IC in human mesangial cells2017

    • Author(s)
      Qiang Liu, Tadaatsu Imaizumi, Hiroshi Tanaka, Yunyan Wu, Tadashi Yoshizawa, Satoko Morohashi, Hiroko Seino, Hiroshi Kijima
    • Organizer
      第106回 日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Dedifferentiated liposarcoma of the pancreas: A case report2017

    • Author(s)
      Tadashi Yoshizawa, Satoko Morohashi, Toshihiro Haga, Hiroko Seino, Yunyan Wu, Hiroshi Kijima
    • Organizer
      第106回 日本病理学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Morphological analysis of the residual rectal mucosa in 12 postoperative ulcerative colitis patients2017

    • Author(s)
      Satoko Morohashi, Masanori Tanaka, Tadashi Yoshizawa, Hiroko Seino, Yunyan Wu, Hiroshi Kijima
    • Organizer
      第106回 日本病理学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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